Potential role of the estrogen receptor gene (ESR1) in anxiety

In addition to neurotransmitters, hormones, acting through the blood stream , also play a role in behavior, To test the potential contribution of genet ic variations in hormone receptors we have examined the association between the alleles of the dinucleotide repeat of the estrogen receptor 1 gene (ES R1) and the nine subscores and total score of the SCL-90 in a group of 179 adult males treated for substance abuse. Based on our prior hypothesis that the length of repeat polymorphisms may play a direct role in gene regulati on, the alleles were divided into two groups, short (S) and long (L), ANOVA of the SS, LS, and LL genotypes showed a significant association at cu les s than or equal to 0.05 for three of the SCL-90 scores: anxiety, phobic anx iety, and total symptoms. Of these the anxiety score remained significant a t a Bonferroni corrected cu of less than or equal to 0.005. By regression a nalysis, the ESR1 gene accounted for 7% of the variance of the anxiety scor e (P less than or equal to 0.0004). These results are consistent with a rol e of the ESR1 gene in human behavior. Since estrogen levels are much higher in women than men, this could account for the increased frequency of anxie ty in women.